Corticotropin-releasing Hormone Directly Activates Noradrenergic Neurons of the Locus Ceruleus Recorded in Vitro

J Neurosci. 2004 Oct 27;24(43):9703-13. doi: 10.1523/JNEUROSCI.2830-04.2004.

Abstract

The neuropeptide corticotropin-releasing hormone (CRH) activates locus ceruleus (LC) neurons, thereby increasing norepinephrine levels throughout the CNS. Despite anatomical and physiological evidence for CRH innervation of the LC, the mechanism of CRH-evoked activation of LC neurons is unknown. Moreover, given the apparent absence of mRNA for CRH receptors in LC neurons, the exact location of action of CRH within the cerulear region is debated. Using in vitro intracellular recordings from rat brainstem, we examined whether CRH exerts a direct effect on LC neurons and which ionic currents are likely affected by CRH. We demonstrate that CRH dose-dependently increases the firing rate of LC neurons through a direct (TTX- and cadmium-insensitive) mechanism by decreasing a potassium conductance. The CRH-evoked activation of LC neurons is, at least in part, mediated by CRH1 receptors and a cAMP-dependent second messenger system. These data provide additional support that CRH functions as an excitatory neurotransmitter in the LC and the hypothesis that dysfunction of the CRH peptidergic and noradrenergic systems observed in patients with mood and anxiety disorders are functionally related.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / physiology*
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Locus Coeruleus / cytology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / physiology*
  • Male
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / physiology*
  • Norepinephrine / physiology*
  • Potassium Channels / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Second Messenger Systems / physiology
  • Synapses / drug effects
  • Synapses / physiology

Substances

  • Potassium Channels
  • Receptors, Corticotropin-Releasing Hormone
  • Corticotropin-Releasing Hormone
  • Norepinephrine